Treatment of vascular endothelial growth factor (vegf) related diseases by inhibition of natural antisense transcript to vegf
AssigneeOPKO CuRNA, LLC
InventorsJoseph Collard, Olga Khorkova Sherman
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Abstract
Oligonucleotide compounds modulate expression and/or function of Vascular Endothelial Growth Factor (VEGF) polynucleotides and encoded products thereof. Methods for treating diseases associated with Vascular Endothelial Growth Factor (VEGF) comprise administering one or more Oligonucleotide compounds designed to inhibit the VEGF natural antisense transcript to patients.
Claims34
A method of modulating function and/or expression of Vascular Endothelial Growth Factor (VEGF) polynucleotide in patient cells or tissues in vivo or in vitro comprising:
- contacting said cells or tissues with an antisense oligonucleotide 5 to 30 nucleotides in length wherein said oligonucleotide has at least 50% sequence identity to a reverse complement of polynucleotide comprising 5 to 30 nucleotides within nucleotides 1 to 643 of SEQ ID NO:
- 2 or nucleotides 1 to 513 of SEQ ID NO:
- 3 (FIG. 3);
- thereby modulating function and/or expression of the Vascular Endothelial Growth Factor (VEGF) polynucleotide in patient cells or tissues in vivo or in vitro.
A method of modulating function and/or expression of an Vascular Endothelial Growth Factor (VEGF) polynucleotide in patient cells or tissues in vivo or in vitro comprising:
- contacting said cells or tissues with an antisense oligonucleotide 5 to 30 nucleotides in length wherein said oligonucleotide has at least 50% sequence identity to a reverse complement of the an antisense of the Vascular Endothelial Growth Factor (VEGF) polynucleotide;
- thereby modulating function and/or expression of the Vascular Endothelial Growth Factor (VEGF) polynucleotide in patient cells or tissues in vivo or in vitro.
A method of modulating function and/or expression of an Vascular Endothelial Growth Factor (VEGF) polynucleotide in patient cells or tissues in vivo or in vitro comprising:
- contacting said cells or tissues with an antisense oligonucleotide 5 to 30 nucleotides in length wherein said oligonucleotide has at least 50% sequence identity to an antisense oligonucleotide to an Vascular Endothelial Growth Factor (VEGF) polynucleotide;
- thereby modulating function and/or expression of the Vascular Endothelial Growth Factor (VEGF) polynucleotide in patient cells or tissues in vivo or in vitro.
A method of modulating function and/or expression of an Vascular Endothelial Growth Factor (VEGF) polynucleotide in patient cells or tissues in vivo or in vitro comprising:
- contacting said cells or tissues with an antisense oligonucleotide that targets a region of the natural antisense of a Vascular Endothelial Growth Factor (VEGF) polynucleotide;
- thereby modulating function and/or expression of an Vascular Endothelial Growth Factor (VEGF) polynucleotide in patient cells or tissues in vivo or in vitro.
A method of modulating an Vascular Endothelial Growth Factor (VEGF) gene expression and/or function in mammalian cells or tissues in vivo or in vitro comprising:
- contacting said cells or tissues with a short interfering RNA (siRNA) oligonucleotide 5 to 30 nucleotides in length specific for an antisense polynucleotide of an Vascular Endothelial Growth Factor (VEGF) polynucleotide wherein said oligonucleotide has at least 50% sequence identity to a complementary sequence of at least about five consecutive nucleic acids of the antisense and/or sense nucleic acid molecule of the Vascular Endothelial Growth Factor (VEGF) polynucleotide;
- and, modulating an Vascular Endothelial Growth Factor (VEGF) gene expression and/or function in mammalian cells or tissues in vivo or in vitro.
A method of modulating an Vascular Endothelial Growth Factor (VEGF) gene expression and/or function in mammalian cells or tissues in vivo or in vitro comprising:
- contacting said cells or tissues with an antisense oligonucleotide of about 5 to 30 nucleotides in length specific for noncoding and/or coding sequences of a sense and/or natural antisense strand of a polynucleotide encoding an Vascular Endothelial Growth Factor (VEGF) molecule wherein an antisense oligonucleotide has at least 50% sequence identity to at least one nucleic acid sequence set forth as SEQ ID NOS:
- 1 to 3;
- and, modulating an Vascular Endothelial Growth Factor (VEGF) gene expression and/or function in mammalian cells or tissues in vivo or in vitro.
A synthetic, modified oligonucleotide comprising at least one modification wherein the modification comprises at least one internucleotide linkage of:
- alkylphosphonate, phosphorothioate, phosphorodithioate, alkylphosphonothioate, phosphoramidate, carbamate, carbonate, phosphate triester, acetamidate, carboxymethyl ester, or combinations thereof, wherein said oligonucleotide is an antisense compound which hybridizes to and modulates expression and/or function of Vascular Endothelial Growth Factor (VEGF) molecules in vivo or in vitro as compared to a control.
A composition comprising one or more oligonucleotides specific for Vascular Endothelial Growth Factor (VEGF) polynucleotides said polynucleotides comprising antisense sequences, complementary sequences, alleles, homologs, isoforms, variants, derivatives, mutants or fragments thereof.
A method of preventing or treating diseases associated with Vascular Endothelial Growth Factor (VEGF) polynucleotides and/or encoded products thereof, comprising:
- administering to a patient a therapeutically effective dose of at least one antisense oligonucleotide that binds to a natural antiense sequence of Vascular Endothelial Growth Factor (VEGF) polynucleotide and modulates expression of said Vascular Endothelial Growth Factor (VEGF) polynucleotides;
- thereby preventing or treating diseases associated with Vascular Endothelial Growth Factor (VEGF) polynucleotides and/or encoded products thereof.
A method of identifying and selecting oligonucleotides for in vivo administration comprising selecting a target polynucleotide associated with a disease state;
- identifying oligonucleotides comprising at least five consecutive nucleotides which are complementary to, or in an antisense orientation to the identified polynucleotide;
- and, measuring the thermal melting point between binding of the antisense oligonucleotide and target polynucleotide under stringent hybridization conditions;
- and, identifying and selecting oligonucleotides for in vivo administration.
Dependencies are inferred from the claim text.